Solid pharmaceutically active implants that provide sustained release of an active ingredient are able to provide a relatively uniform concentration of active ingredients in the body. Implants are particularly useful for providing a high local concentration at a particular target site for extended periods of time. These sustained release forms reduce the number of doses of the drug to be administered, and avoid the peaks and troughs of drug concentration found with traditional drug therapies. Use of a biodegradable drug delivery system has the further benefit that the spent implant need not be removed from the target site.
Many of the anticipated benefits of delayed release implants are dependent upon sustained release at a relatively constant level. However, formulations of hydrophobic drugs with biodegradable matrices may have a release profile which shows little or no release until erosion of the matrix occurs, at which point there is a dumping of drug.
The eye is of particular interest when formulating implantable drugs, because one can reduce the amount of surgical manipulation required, and provide effective levels of the drug specifically to the eye. When a solution is injected directly into the eye, the drug quickly washes out or is depleted from within the eye into the general circulation. From the therapeutic standpoint, this may be as useless as giving no drug at all. Because of this inherent difficulty of delivering drugs into the eye, successful medical treatment of ocular diseases is inadequate.
Improved sustained release formulations which allow for a constant drug release rate are of considerable interest for medical and veterinary uses.
Relevant Literature
U.S. Pat. Nos. 4,997,652 and 5,164,188 disclose biocompatible implants for introducing into an anterior chamber or posterior segment of an eye for the treatment of an ocular condition.
Heller, Biodegradable Polymers in Controlled Drug Delivery, in: CRC Critical Reviews in Therapeutic Drug Carrier Systems, Vol. 1, CRC Press, Boca Raton, Fla., 1987, pp 39–90, describes encapsulation for controlled drug delivery. Heller in: Hydrogels in Medicine and Pharmacy, N. A. Peppes ed., Vol. III, CRC Press, Boca Raton, Fla., 1987, pp 137–149, further describes bioerodible polymers.
Anderson et al., Contraception (1976) 13:375 and Miller et al., J. Biomed. Materials Res. (1977) 11:711, describe various properties of poly(dL-lactic acid). U.S. Pat. No. 5,075,115 discloses sustained release formulations with lactic acid polymers and co-polymers.
Di Colo (1992) Biomaterials 13:850–856 describes controlled drug release from hydrophobic polymers.